Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy
Authors: Jicheng Lv, Muh Geot Wong, Michelle A. Hladunewich, Vivekanand Jha, Lai Seong Hooi, Helen Monaghan, Minghui Zhao, Sean Barbour, Meg J. Jardine, Heather N. Reich, Daniel Cattran, Richard Glassock, Adeera Levin, David C. Wheeler, Mark Woodward, Laurent Billot, Sandrine Stepien, Kris Rogers, Tak Mao Chan, Zhi-Hong Liu, David W. Johnson, Alan Cass, John Feehally, Jürgen Floege, Giuseppe Remuzzi, Yangfeng Wu, Rajiv Agarwal, Hong Zhang, Vlado Perkovic, Mona Razavian, Martin Gallagher, Frances Daley, Samantha Hand, Helen Knight, Sarah Gallagher, Bhadran Bose, Craig Lawlor, Junie McCourt, Chen Au Peh, Eileen Scott, Robert Carroll, Toby Coates, Bronwyn Hockley, Megan Hockley, Jenny Latte, Kathy Nicholls, Michael Cai, Paul Champion de Crespigny, Therese Cronin, Maria Farrell, Peter Hughes, Rosemary Masterson, Gloria Sepe, Sven-Jean Tan, Nigel Toussaint, Rachel Wollstencroft, Bruce Cooper, Marjorie Chang, Helen Clayton, Stephanie Tan, Heidi Tsang, Joanna Sudak, Louis P Laurin, Vincent Pichette, Karine Chausse, Martine Comeau, Lucy Lepine, Marie Soliel, Stephanie Beauchemin, Emilie René, Marceline Quach, Karine Daoust, Ariane Lessard, Maude Bachand-Fournier, Marysa Bétournay, Marie-Soleil Paradis, Mukelda Mikye Castor, Susan Huang, Louise Moist, Kerri Gallo, Rachel VanWesenbeeck, Teresa Longfield, Faith Norris, Amy Moyer, Zabrina Bailey Lozon, Matthew Miller, Catherine Clase, Christian Rabbat, Madison Salisbury, Andrea Mazzetti  Vieira, Faraz Lalji, Cathy Moreau, Neesh Pannu, Ainslie Hildebrand, Nancy Ruholl, Nasreen Ahmad, Maliha Muneer, Louise Girard, Michelle Catherine Mann, Brenda Hemmelgarn, Braden Manns, Pietro Ravani, Shelia Li, Janice Mackay, Sharon Gulewich, Zainab Sheriff, Jack Ferera, Katy Vela, Anny Gonzalez, Arti Bhasin, Ping Lam, Fatima Haji, Sufang Shi, Lijun Liu, Yunfei Bao, Guilli Sui, Caili Wang, Zengyan Li, Li Lv, Lan Yang, Haitao Li, Zhangsuo Liu, Junjun Zhang, Bo Huang, Yang Yang, Shuxia Fu, Shaomei Li, Huaying Pei, Limin Zhang, Ning Lu, Jifang Xu, Longyun Xu, Qian Yang, Jingwei Jin, Nan Chen, Weiming Wang, lili Xu, Ziru Xia, Huan Xu, Wei Huang, Yiwen Mo, Weihong Chen, Lihua Wang, Rongshan Li, Shulei Yao, Xiaoxia Li, Zhaohui Ni, Ling Wang, Leyi Gu, Huihua Pang, Yin Zhou, Yan Jin, Haitao Zhang, Xia Wang, Weibo Le, Jinhua Hou, Xia Song, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Yu Shi, Jianshe Liu, Chun Zhang, Cheng Wan, Shan Chen, Hongyan Zhu, Fang Tang, Hui Li, Xuan Jiang, Mei Wang, Li Zuo, Yu Yan, Bao Dong, Yina Wang, Xuan Zhang, Li Bai, Peng Li, Dong Qi, Zhiying Cai, Guisen Li, Li Wang, Kung Peng, Daqing Hong, Daqing Yao, Aihua Jiang, Qiong Luo, Shuang Hou, Fan Zhang, Lei Zheng, Yuanchang Luo, Guangyan Cai, Shuwei Duan, Yan Zhang, Shuang Liang, Xiaolei Shao, Rong Wang, Xiang Liu, Ying Xu, Jing Zhang, Jianghua Chen, Jun Cheng, Lingfei Zhao, Xiaoying Du, Hongyu Chen, Bin Zhu, Weili Pan, Yalong Ma, Chenmin Cui, Qingxiao Zhang, Jiawei Zhang, Ping Fu, Xi Tang, Wei Qin, Yaping Liang, Detian Li, Guangping Sun, Xiaoxiao Su, Baixue Zhao, Qiang He, Xiaogang Shen, Danna Zheng, Yi Sun, Hua Zheng, Wei Zheng, Fuming Lu, Lingyun Lai, Minmin Zhang, Ningxin Xu, Huizhu Shi, Wangsheng Chen, Xinling Liang, Zhiming Ye, Lixia Xu, Ruijing Zhang, Yiming Tao, Dongmei Xu, Lijun Tang, Xiuhua Lian, Guohua Ding, Huiming Wang, Lihua Yang, Zhengkang Li, Zhao Hu, Bei Jiang, Zhiling Guo, Jie Chang, Qingmiao Wang, Nan Li, Aiping Zhang, Shumei Shi, Zhen Li, Hong Xu, Beiyan Bao, Yu Zhao, Zhuan Nie, Ting Liu, Yue Wang, Zhen Cui, Chunyan Su, Li Gong, Guoping Liu, Lei Yu, Bo Wang, Dan Xu, Ying Li, Qiongzhen Lin, Ke Yu, Yipu Shen, Hong Cheng, Xiaoyi Xu, Yu Wang, Rong Liu, Gang Xu, Min Han, Le Wang, Changying Xing, Chengning Zhang, Zhiming Huang, Guang Yang, Xueqiang Xu, Xiaolin Lv, Huiping Hong, Bing Liu, Lin Tao, Xiaoxuan Zhang, Huijie Yang, Xiaochun Yang, Xiaodong Zhang, H Yang, Yonghui Mao, Hua Wu, Tianhui Li, Haitao Wang, Ban Zhao, Hongli Lin, Ning Yang, K Samuel Fung, R Chan, Rebecca Law, Sreelatha Melemadathil, Hijaz PT, Rahila Razak, K C Sinta, Gopalakrishnan Natarajan, Junaith Mohammed, Dinesh K Thanigachalam, Sreebhushan R Devaraju, Satheesh Reddy Alavala, Anvesh Golla, Vamsi Nagalla, Raju Nallagasu, Manisha Sahay, Sravani Borra, Rakesh Sahay, LV Krishna Suri Dasyam, Mounika Kumbagiri, Prasad MSLN, Arfa Nazneen, KVL Prathyusha, Raja Ramachandran, Krishan L Gupta, Thakaur Sain, Narayan Prasad, Dharmendra S Bhaduria, Ashok K Pandy, Pratik Singh, Mohamad Z Abdul Wahab, Zurina Che Rohani, Haiyuni Mohd Yassim, Siti Nur Omaira Razali, Norhaslinda Saaidi, Wan Mohamad Wan Hazlina, Rosnawati Yahya, Seow Yeing Yee, Nurul Zaynah, Nurul Hizwani Azahar, Hui Foong Tan, Chek Loong Loh, Saliza Hashim, Yee Yan Lee, Xin Jie Lim, Norlia Mohd Khairi, Sridhar Ramanaidu, Kah Mean Thong, Wen Jiun Liu, Lik Wee Ee, Yuana Mohd Yusoff, Laura Lui Sian Ngu, Nyuk Suan Chai, Lawrence Wei Soon Hii, Clare Hui Hong Tan, Sharifah Hatijah Wan Japar, Lily Mushahar, Siti Hawa Md Yusuff, Maisarah Noor, Kok Peng Ng, Soo Kun Lim, Wan Ahmad Faizal Alaidin Razali, Wan Ahmad Hafiz Wan Md Adnan, David Jayne, Tom Greene, Michael Walsh, Angela Yee-Moon Wang, Amanda Mather, Amanda Y Wang
Journal: JAMA (2022)

The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain.To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline.An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021.Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group).The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure.Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]).Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy.ClinicalTrials.gov Identifier: NCT01560052.